F477
Liver Disease

hepatitis and liver disease | pyrrolizidine alkaloid toxicity | liver flukes | liver abscesses

Introduction: In order to understand diseases of the liver, it is important to have some knowledge of the normal function of this complicated organ. The liver is important in keeping the body’s metabolism and function in balance. It has been estimated that the liver is responsible for over 1,500 essential processes on a biochemical level. The failure of any of these biochemical functions could lead to death of the animal.

Some of the main functions of the liver include proper handling of carbohydrates (sugars, starches), lipids (fats, cholesterol, bile acids), and proteins. Some of the important proteins produced by the liver include blood clotting factors, urea (used by the kidney to help with the body’s water preservation), and albumin (the main protein in the blood which helps maintain the proper fluid volume in the heart and blood vessels). Essential vitamins and minerals are produced, stored, or altered by the liver for proper use in the body. The liver aids in the functions of the immune system, the endocrine system, and in maintaining healthy blood cells. Bile acids are produced and stored in the liver and gallbladder, and are used in the digestive tract in the breakdown of food.

One very important function of the liver is its role as the body’s filter from the digestive tract. The entire digestive tract contains bacteria and food in various stages of breakdown. Nutrients are absorbed into the blood through tiny capillaries from the stomach and intestines. Blood from the digestive tract may be thought of as "dirty," since it is so close to a source of contamination— millions of bacteria and possibly harmful substances taken into the body through the mouth. From here, the blood enters the liver’s portal blood system, where the liver can "detoxify" any harmful substances and acts as the first line of defense against invading bacteria.

A specific condition called hepatic encephalopathy (HE) often develops with diseases in which the liver’s function as a filter fails. "Hepatic encephalopathy" actually means disease of the brain associated with the liver. HE occurs when toxic by-products, usually filtered by the liver, arrive at high levels in the brain via the bloodstream. These by-products of digestion, especially ammonia, cause hallucination-like symptoms to occur in the brain along with circling or pacing, aggression, blindness that seems to come and go, "head pressing" (standing with the head lowered and pressed into a corner or against a wall), and hepatic comas. Cattle have also been known to vocalize excessively.

The liver has a tremendous ability for regeneration and functional reserve. It is able to tolerate injury and insult better than most organs without failing (although sickness may be very apparent in the body) and can repair itself remarkably well following damage. These are wonderful features of this vital organ, but they can also make it difficult to recognize when a serious disease of the liver is present.

Introduction: Liver disease occurs when the liver becomes inflamed (called hepatitis) or injured in some way. Liver disease can be the result of a one time event or can be the result of continued injury or inflammation over an extended period of time. Liver failure occurs when approximately 75% of the liver tissue becomes damaged over time or is damaged at one time. This amount of damage exceeds the liver’s functional reserve and leads to clinical signs of liver failure.

Causative Agents: Some of the possible causes of liver disease include the following:

1. Black Disease (Clostridium novyi): In black disease, toxins produced by the bacteria cause infectious necrotic hepatitis. The black disease infection will usually begin as a result of liver fluke (Fasciola hepatica) infestations that damage the liver and allow the right environment for the Clostridium novyi bacteria to overgrow. Additional details about black disease can be found on page F120.
2. Bacillary Hemoglobinuria or "red water" (Clostridium hemolyticum): Bacillary hemoglobinuria is another clostridial disease that affects the liver. Like black disease, bacillary hemoglobinuria infections will usually begin as a result of liver fluke (Fasciola hepatica) infestations that damage the liver and allow the right environment for the Clostridium hemolyticum bacteria to overgrow. Additional details about this disease can be found on page F120.
3. The administration or consumption of toxic drugs or poisons:
   1. Since the liver is the first organ to handle any drug taken orally, an overdose of many drugs can cause liver failure. Some drugs which have been known to cause acute liver failure include inhaled anesthetic gases, some anticonvulsants, tetracycline, and trimethoprim-sulfa antibiotics.
   2. Poisonous substances and plants can also damage the liver. Some of these include pyrrolizidine-alkaloid containing plants, blue-green algae, aflatoxin, moldy alfalfa, and heavy metals (iron, copper).

Clinical Signs: Clinical signs of liver disease are usually dramatic, but often not specific. Signs of hepatic encephalopathy (discussed previously) are often noticed and may be profound, with severe depression and disorientation. Other signs that are sometimes seen include dehydration, weight loss, diarrhea, ascites (fluid buildup under the skin), pruritus (itching), and photosensitization. Jaundice or icterus (a yellowness to the gums and white of the eye) is sometimes present. In the most severe cases, the animal may experience hemophilia (bleeding tendencies due to a loss of blood-clotting ability). Widespread damage to the liver that is not immediately life-threatening may lead to chronic liver failure if there remains too little healthy tissue to regenerate.

Diagnosis: Diagnosis of liver disease is accomplished with a variety of tests. Physical examination by a veterinarian, followed by routine CBC, serum chemistry panel, and urinalysis are generally performed first. An increase in the liver enzymes gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) often indicate a liver problem. Serum bile acid and bilirubin testing is generally recommended with any liver disease. For a complete diagnosis to be made, a liver biopsy can be obtained and examined by a veterinary pathologist.

Treatment: Treatment of liver disease centers around aggressive supportive care and eliminating the cause of the failure, if possible. Discontinuing any drug which has potentially caused the liver to fail is essential. Fluid therapy and slow correction of the blood acid-base balance and dissolved salt levels (sodium, potassium, chloride) must be initiated as soon as possible. If hepatic encephalopathy is present, this condition must be specifically treated by reducing ammonia levels in the bloodstream. Laxatives (mineral oil), lactulose, and oral medications can be given to help reduce ammonia levels in the blood. Antibiotics (neomycin) are selected specifically for their ability to decrease ammonia-producing bacteria. Diet therapy is started as soon as possible. Diets that are restricted in proteins are very important in recovery and are usually fed initially in small amounts, several times daily. Treatment may continue for weeks to months, and can even be indefinite in some cases in order to prevent recurrence of the liver failure. Animals that will not eat must be force fed. A gruel may be administered to cattle by orogastric tube or rumen fistula. Mixing normal rumen fluid with alfalfa-meal (15% protein) and dried brewers’ grain or beet pulp with potassium chloride is recommended. Transfaunation (a process which takes the rumen juices from a healthy animal and places them in a sick animal) may stimulate appetite and help return a sick cow’s rumen back to normal.

Depending on the cause of the liver failure, additional treatments are sometimes utilized. These would include the use of antibiotics (ceftifur, penicillin, trimethoprim-sulfa), vitamin B, folic acid, and vitamin K.

Prognosis: Prognosis for recovery depends on how severe the injury to the liver has been, on the ability to remove any contributing cause of the disease, and on the general health of the animal. Older animals in poor body condition may experience failure of multiple organs together with a relatively moderate injury to the liver; however, a younger calf in good health that experiences the same injury to the liver may be able to fully recover with proper treatment. Generally speaking, if the cow is not eating, continues to be in constant acidosis, or does not respond to initial treatments, the prognosis is poor.

Introduction: This liver condition occurs when livestock consume plants that contain pyrrolizidine alkaloid (PA). The effects of PA toxicity are cumulative, meaning that the toxic dose of the plants does not have to be consumed at one time to cause liver damage. Some animals suffer liver damage or even death after consuming one large dose of PA, while others will continue to consume small, but damaging, amounts of PA until a "threshold" has been met and clinical signs of problems result.

Clinical Signs: The signs noticed with pyrrolizidine alkaloid (PA) toxicity are associated directly with the damage it causes in the liver. Signs that are commonly noticed include dehydration, weight loss, diarrhea, ascites (fluid buildup under the skin), and prolapsed rectum. Behavioral changes and neurological signs are also sometimes noticed in cattle.

Diagnosis: Suspected cases of pyrrolizidine alkaloid (PA) toxicity can be identified when elevated liver enzymes are detected in a blood sample. Serum bile acid and bilirubin levels are also elevated. A liver biopsy is one of the best ways of determining if PA toxicity is the cause. If the animal has already died because of PAs, necropsy findings will also help to determine the cause. At necropsy, the liver is small, firm, and pale brown to yellow. Samples of the animal’s feed can also be analyzed for the presence of PA containing plants.

Treatment: The treatment options for liver disease associated with pyrrolizidine alkaloid (PA) toxicity depends on the severity of the liver damage. If the cow has been consuming significant amounts of PAs over a period of time and has significantly damaged the liver to the point of fibrosis, treatment is not beneficial. However, if the liver is only mildly irritated or damaged, the liver can repair itself and return to a relatively normal state. A detailed description of the treatment options for liver disease can be found on F477 page 3.

Here is a list of some of the plants that are known to cause pyrrolizidine alkaloid toxicity:

Introduction/Causative Agents: Fasciola hepatica, Fascioloides magna (giant liver fluke), and Dicrocoelium dendriticum are the most common liver flukes found in cattle in the United States. Infections of Fasciola hepatica are by far the most common of the three. The life cycle of F. hepatica begins when eggs from an infected animal are shed in the manure. The eggs will develop into miracidia stage flukes that infect snails. While in the snail, the liver fluke develops into a metacercariae stage. The metacercariae are then spread by snails and become encysted on plant vegetation that is later consumed by cattle.

Once ingested, immature flukes will exit the intestine and migrate through the animal’s body damaging tissues and organs. The most common organ that is damaged is the liver. The flukes will cause hemorrhage, fibrosis (scaring), calcification, and inflammation in the liver. The damaged liver tissue creates the perfect environment for clostridial bacteria to overgrow and cause disease (See black disease and red water on page F120).

Clinical Signs/Diagnosis: Weight loss, lethargy, dehydration, ascites (fluid accumulation), anemia (loss of red blood cells), and rough hair coat are common signs. Many of these are the typical signs mentioned previously in the hepatitis and liver disease section. Liver fluke infestations can be identified by finding fluke eggs in manure samples, through blood testing (finding antibodies or antigen), or by actually finding the flukes during a necropsy exam. Fecal flotation techniques for finding fluke eggs can be complicated, so attention to test instructions is a must.

Treatment/Prevention: In the ideal situation, liver flukes can be controlled on three different fronts. First and foremost, internal fluke infections should be eliminated from the animal. Secondly, control measures should be taken to remove the snail populations that help to perpetuate the infections. Lastly, animals should be kept away from areas that harbor large snail populations. On most operations, only the first measure mentioned above is routinely used. This is often because many of the products used to control snails (copper sulfate and sodium pentachlorophenate) are very toxic to certain animals and fish. It is also very difficult to adequately fence off large areas of pasture that may contain snails. As a result, most producers focus on using clorsulon or albendazole, the only two products currently approved in the United States to control liver flukes. Products like Ivomec Plus that contain ivermectin and clorsulon can also be used to control flukes.

Determining when these products should be used can be a challenging issue and should be based on local environmental conditions, snail populations, current infection levels, and previous exposure. Because of this, it is difficult to recommend one type of control program to fit all operations. As a starting point, most operations will use some form of twice-a-year treatment. For example, along the Gulf coast of the United States cattle are often treated just prior to the fall rainy season and again in the late spring. On the other hand, cattle in the northwestern United States are treated after they are pulled off pasture and then again in January or February. These are often the minimum recommendations, and more frequent treatments are required in the mild climates.

Clinical Signs: The signs associated with liver abscesses often go unnoticed, particularly if the abscess has isolated itself from the rest of the body. Occasionally, the only noticeable sign will be a decreased rate of gain. In animals that have large or multiple abscesses, the signs can be more obvious. Common signs include weight loss, lack of appetite, fever, and decreased milk production. Some animals may appear to be in pain and have trouble getting up and down. If the abscesses spread and damage blood vessels, difficulty breathing, septic shock, bleeding from the mouth or nose, and sudden death can result. These animals are often sick, have a fever, and deteriorate rapidly.

Diagnosis: Often it can be difficult to identify cattle with small abscesses in the liver. Sometimes blood work and ultrasound can be used to help identify problem animals. Most cases of liver abscesses go undiagnosed until slaughter.

Treatment/Prevention: Treatment for liver abscesses can include antibiotics such as penicillin or tetracycline; however, these treatments are often not completely successful. Because of this, most efforts should focus on preventing the problem. Efforts can include treating for liver flukes, introducing cattle to high concentrate diets more slowly over a period of weeks (this helps prevent acidosis), feeding low levels of antibiotics in the feed, and preventing any type of bacterial infection (navel ill, metritis, abrasions, etc.).